A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children

Ji Hyun Lee, Kyung Won Kim, Heon Yung Gee, Jaechun Lee, Keun Hwa Lee, Hae Sim Park, Seung Hyun Kim, So Won Kim, Mi Na Kim, Kyu Earn Kim, Kyung Hwan Kim, Min Goo Lee, Myung Hyun Sohn

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Abstract

Background: Atopic diseases are the most common chronic diseases of childhood, and the genetics of atopy are complex and heterogeneous. Protease-activated receptor-2 (PAR-2) is involved in various inflammatory diseases, but the association of PAR-2 with allergic diseases remains unclear. Objective: To examine the contribution of genetic variation of PAR-2 to atopic phenotypes in the Korean childhood cohort. Methods: We identified PAR-2 variations in a Korean population and conducted association analyses by using 316 unrelated atopic and 210 nonatopic subjects. We analyzed serum IgE and total eosinophil count levels and examined PAR-2 mRNA and protein expression levels. Results: In the case-control association analysis, atopy was significantly associated with a single c.621C>T (p.I207I, rs631465) polymorphism of PAR-2 (P =.001, odds ratio = 1.95). Subjects with the c.621T risk allele had significantly higher serum IgE (P =.004) and total eosinophil count (P = .03) levels. Moreover, the positive association of c.621T was reproduced in the replication study (P =.01, joint P value of the replication < .001). An in silico analysis of RNA secondary structure prediction revealed that the C to T conversion at c.621 greatly increased predicted PAR-2 mRNA stability. This was also confirmed by an in vitro assay for mRNA stability. Furthermore, following an in vivo approach on gene expression in PBMCs showed that the expression levels of PAR-2 mRNA and protein in subjects with the c.621CT or TT genotype were significantly higher than in those with the c.621CC genotype. Conclusions: These results indicate that the synonymous c.621C>T polymorphism in PAR-2 might be associated with the risk of atopy, potentially by altering PAR-2 gene expression.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Volume128
Issue number6
DOIs
Publication statusPublished - 2011 Jan 1

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PAR-2 Receptor
Eosinophils
Immunoglobulin E
Serum
Chronic Disease
Joints
Alleles
Odds Ratio
Phenotype
Gene Expression
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Lee, Ji Hyun ; Kim, Kyung Won ; Gee, Heon Yung ; Lee, Jaechun ; Lee, Keun Hwa ; Park, Hae Sim ; Kim, Seung Hyun ; Kim, So Won ; Kim, Mi Na ; Kim, Kyu Earn ; Kim, Kyung Hwan ; Lee, Min Goo ; Sohn, Myung Hyun. / A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children. In: Journal of Allergy and Clinical Immunology. 2011 ; Vol. 128, No. 6.
@article{7d8d218e2b9848b493b956c1c064c123,
title = "A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children",
abstract = "Background: Atopic diseases are the most common chronic diseases of childhood, and the genetics of atopy are complex and heterogeneous. Protease-activated receptor-2 (PAR-2) is involved in various inflammatory diseases, but the association of PAR-2 with allergic diseases remains unclear. Objective: To examine the contribution of genetic variation of PAR-2 to atopic phenotypes in the Korean childhood cohort. Methods: We identified PAR-2 variations in a Korean population and conducted association analyses by using 316 unrelated atopic and 210 nonatopic subjects. We analyzed serum IgE and total eosinophil count levels and examined PAR-2 mRNA and protein expression levels. Results: In the case-control association analysis, atopy was significantly associated with a single c.621C>T (p.I207I, rs631465) polymorphism of PAR-2 (P =.001, odds ratio = 1.95). Subjects with the c.621T risk allele had significantly higher serum IgE (P =.004) and total eosinophil count (P = .03) levels. Moreover, the positive association of c.621T was reproduced in the replication study (P =.01, joint P value of the replication < .001). An in silico analysis of RNA secondary structure prediction revealed that the C to T conversion at c.621 greatly increased predicted PAR-2 mRNA stability. This was also confirmed by an in vitro assay for mRNA stability. Furthermore, following an in vivo approach on gene expression in PBMCs showed that the expression levels of PAR-2 mRNA and protein in subjects with the c.621CT or TT genotype were significantly higher than in those with the c.621CC genotype. Conclusions: These results indicate that the synonymous c.621C>T polymorphism in PAR-2 might be associated with the risk of atopy, potentially by altering PAR-2 gene expression.",
author = "Lee, {Ji Hyun} and Kim, {Kyung Won} and Gee, {Heon Yung} and Jaechun Lee and Lee, {Keun Hwa} and Park, {Hae Sim} and Kim, {Seung Hyun} and Kim, {So Won} and Kim, {Mi Na} and Kim, {Kyu Earn} and Kim, {Kyung Hwan} and Lee, {Min Goo} and Sohn, {Myung Hyun}",
year = "2011",
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Lee, JH, Kim, KW, Gee, HY, Lee, J, Lee, KH, Park, HS, Kim, SH, Kim, SW, Kim, MN, Kim, KE, Kim, KH, Lee, MG & Sohn, MH 2011, 'A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children', Journal of Allergy and Clinical Immunology, vol. 128, no. 6. https://doi.org/10.1016/j.jaci.2011.06.036

A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children. / Lee, Ji Hyun; Kim, Kyung Won; Gee, Heon Yung; Lee, Jaechun; Lee, Keun Hwa; Park, Hae Sim; Kim, Seung Hyun; Kim, So Won; Kim, Mi Na; Kim, Kyu Earn; Kim, Kyung Hwan; Lee, Min Goo; Sohn, Myung Hyun.

In: Journal of Allergy and Clinical Immunology, Vol. 128, No. 6, 01.01.2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children

AU - Lee, Ji Hyun

AU - Kim, Kyung Won

AU - Gee, Heon Yung

AU - Lee, Jaechun

AU - Lee, Keun Hwa

AU - Park, Hae Sim

AU - Kim, Seung Hyun

AU - Kim, So Won

AU - Kim, Mi Na

AU - Kim, Kyu Earn

AU - Kim, Kyung Hwan

AU - Lee, Min Goo

AU - Sohn, Myung Hyun

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Background: Atopic diseases are the most common chronic diseases of childhood, and the genetics of atopy are complex and heterogeneous. Protease-activated receptor-2 (PAR-2) is involved in various inflammatory diseases, but the association of PAR-2 with allergic diseases remains unclear. Objective: To examine the contribution of genetic variation of PAR-2 to atopic phenotypes in the Korean childhood cohort. Methods: We identified PAR-2 variations in a Korean population and conducted association analyses by using 316 unrelated atopic and 210 nonatopic subjects. We analyzed serum IgE and total eosinophil count levels and examined PAR-2 mRNA and protein expression levels. Results: In the case-control association analysis, atopy was significantly associated with a single c.621C>T (p.I207I, rs631465) polymorphism of PAR-2 (P =.001, odds ratio = 1.95). Subjects with the c.621T risk allele had significantly higher serum IgE (P =.004) and total eosinophil count (P = .03) levels. Moreover, the positive association of c.621T was reproduced in the replication study (P =.01, joint P value of the replication < .001). An in silico analysis of RNA secondary structure prediction revealed that the C to T conversion at c.621 greatly increased predicted PAR-2 mRNA stability. This was also confirmed by an in vitro assay for mRNA stability. Furthermore, following an in vivo approach on gene expression in PBMCs showed that the expression levels of PAR-2 mRNA and protein in subjects with the c.621CT or TT genotype were significantly higher than in those with the c.621CC genotype. Conclusions: These results indicate that the synonymous c.621C>T polymorphism in PAR-2 might be associated with the risk of atopy, potentially by altering PAR-2 gene expression.

AB - Background: Atopic diseases are the most common chronic diseases of childhood, and the genetics of atopy are complex and heterogeneous. Protease-activated receptor-2 (PAR-2) is involved in various inflammatory diseases, but the association of PAR-2 with allergic diseases remains unclear. Objective: To examine the contribution of genetic variation of PAR-2 to atopic phenotypes in the Korean childhood cohort. Methods: We identified PAR-2 variations in a Korean population and conducted association analyses by using 316 unrelated atopic and 210 nonatopic subjects. We analyzed serum IgE and total eosinophil count levels and examined PAR-2 mRNA and protein expression levels. Results: In the case-control association analysis, atopy was significantly associated with a single c.621C>T (p.I207I, rs631465) polymorphism of PAR-2 (P =.001, odds ratio = 1.95). Subjects with the c.621T risk allele had significantly higher serum IgE (P =.004) and total eosinophil count (P = .03) levels. Moreover, the positive association of c.621T was reproduced in the replication study (P =.01, joint P value of the replication < .001). An in silico analysis of RNA secondary structure prediction revealed that the C to T conversion at c.621 greatly increased predicted PAR-2 mRNA stability. This was also confirmed by an in vitro assay for mRNA stability. Furthermore, following an in vivo approach on gene expression in PBMCs showed that the expression levels of PAR-2 mRNA and protein in subjects with the c.621CT or TT genotype were significantly higher than in those with the c.621CC genotype. Conclusions: These results indicate that the synonymous c.621C>T polymorphism in PAR-2 might be associated with the risk of atopy, potentially by altering PAR-2 gene expression.

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U2 - 10.1016/j.jaci.2011.06.036

DO - 10.1016/j.jaci.2011.06.036

M3 - Article

VL - 128

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 6

ER -